Advanced glycation end products (AGEs) are cross-linked polymers irreversibly formed by a series of reactions starting from a nonenzymatic reaction between carbonyl groups of reducing sugars such as glucose and amino groups of proteins (i.e. Maillard reaction). These reactions are gradually proceed in a living body over a long period. For example, hemoglobin AlC (HbAlc), a kind of AGEs, which is one of laboratory test indicators of diabetes is a glycation product of hemoglobin that is a protein of erythrocyte.
AGEs are causative substance of diabetes complications such as diabetic retinopathy and diabetic nephropathy. AGEs are also known to be associated with a crisis of diabetic angiopathy through binding to a specific receptor (RAGE) on vascular endothelial cells. Considering the report which indicates that in Japan, now, the number of patients potentially suffered form diabetes is increased up to 16,300,000 and in particular, one person per 4.5 middle-aged and older persons is in a prestage of a diabetes, removing AGEs from the living body is a very important for preventing crisis and progression of diabetes complication in the future. In addition, AGEs are associated with a crisis of debilitating disease such as atherosclerosis, Alzheimer's disease and arthritis rheumatoides.
Various kinds of drugs are proposed for removing AGEs from the human body. For example, so far, aminoguanidine derivatives and pyridoxamine derivatives have been known as inhibitors of AGEs formation. In addition, JP-A-2004-300153 have declared 3-methyl-1-phenyl-2-pyrazoline-5-on as the inhibitor. Although those inhibitors of AGEs formation are effective for preventing further accumulation of AGEs, those can not resolve a problem that is to remove already accumulated AGEs.
On the other hand, substances such as N-phenacylthiazolium bromide (PTB) which can break an established AGE-linkage have been studied. Recently, seven compounds including 1,4-benzene-bis[4-methyleneaminophenoxyisobutyric acid] that have the function are reported (e.g. JP-A-2004-529126). The AGE-degradation activities of those substances, however, are not sufficiently potent.
So far, any drugs which are effective for the elimination of accumulated AGEs has not been developed.
The present inventor developed a copolymer resin comprising hydrophilic methacrylate and found that the resin has an excellent ability to adsorb phosphoric acid and oxalic acid (see JP-A-2005-13.9414). Any use of the resin other than the above adsorption ability, however, is still not known.